U.S. patent application number 16/068514 was filed with the patent office on 2019-01-03 for procoagulant factors suitable for subsequent autologous use.
The applicant listed for this patent is REAPPLIX APS. Invention is credited to Niels Erik HOLM, Rasmus LUNDQUIST.
Application Number | 20190000367 16/068514 |
Document ID | / |
Family ID | 59273653 |
Filed Date | 2019-01-03 |
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United States Patent
Application |
20190000367 |
Kind Code |
A1 |
LUNDQUIST; Rasmus ; et
al. |
January 3, 2019 |
PROCOAGULANT FACTORS SUITABLE FOR SUBSEQUENT AUTOLOGOUS USE
Abstract
Provided is a blood collection unit suitable for accelerated
blood coagulation of whole blood for subsequent autologous or
allogeneic use. The blood collection unit includes an inside
surface that an activation site accelerating coagulation by having
a high roughness. Further provided is a blood collection unit
including an inside surface that has an activation site having a
high roughness area, and an interior of the blood collection unit
has been prepared with a pressure of no more than 255 mBar, and
preferably a pressure of no more than 130 mBar.
Inventors: |
LUNDQUIST; Rasmus;
(Bronshoj, DK) ; HOLM; Niels Erik; (Birkerod,
DK) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
REAPPLIX APS |
Birkerod |
|
DK |
|
|
Family ID: |
59273653 |
Appl. No.: |
16/068514 |
Filed: |
January 6, 2017 |
PCT Filed: |
January 6, 2017 |
PCT NO: |
PCT/EP2017/050263 |
371 Date: |
July 6, 2018 |
Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61B 5/150351 20130101;
A61B 5/150099 20130101; A61B 5/150389 20130101; A61B 5/150274
20130101; A61B 5/150473 20130101; A61B 5/15003 20130101; B01L
3/5082 20130101; A61B 5/150755 20130101; G01N 33/491 20130101; A61B
5/154 20130101; A61B 5/150503 20130101; B01L 3/505 20130101; A61B
5/1438 20130101 |
International
Class: |
A61B 5/15 20060101
A61B005/15 |
Foreign Application Data
Date |
Code |
Application Number |
Jan 6, 2016 |
EP |
16150311.5 |
Jan 14, 2016 |
DK |
PA 2016 70017 |
Claims
1-12. (canceled)
13. A blood collection unit suitable for accelerated blood
coagulation of whole blood for subsequent autologous or allogeneic
use, comprising: an outer wall comprising a closed bottom end, an
open top end, a side wall spanning between the ends, and a stopper
for insertion into the open end to releasably seal the blood
collection container, the stopper having a puncturable self-sealing
septum or valve, an inner volume at least partially bounded by an
inside surface of the outer wall, and a procoagulant environment,
wherein the inner volume is prepared with a pressure of no more
than 131.72 m Bar.
14. The blood collection unit according to claim 13, the blood
collection unit further comprising: an activation site formed on
the inside surface or formed on an insert in the inner volume of
the blood collection unit, where the activation site has a
roughness, R.sub.RMS, of at least 0.012 .mu.m.
15. The blood collection unit according to claim 14, wherein the
activation site has a roughness, R.sub.RMS, of at least 0.4
.mu.m.
16. The blood collection unit according to claim 14, wherein the
activation site is hydrophobic.
17. The blood collection unit according to claim 13, where the
inside surface is hydrophobic.
18. The blood collection unit according to claim 13, wherein the
blood collection unit is made of a hydrophobic material.
19. The blood collection unit according to claim 13, wherein the
inside surface has not been corona treated.
20. The blood collection unit according to claim 13, wherein the
inside surface has been corona treated.
21. The blood collection unit according to claim 13, wherein the
blood collection unit is a tube or a double-ended needle.
22. The blood collection container according to claim 13, wherein
the inner volume is prepared with a pressure of no more than 100
mBar.
23. The blood collection container according to claim 13, wherein
the inner volume is prepared with a pressure of no more than 81.06
mBar.
24. The blood collection container according to claim 13, wherein
the inner volume is prepared with a pressure of no more than 50.66
mBar.
25. The blood collection container according to claim 13, wherein
the inner volume is prepared with a pressure of no more than 20.27
mBar.
Description
BACKGROUND OF THE DISCLOSURE
1. Field of the Disclosure
[0001] The present invention relates to a method, apparatus and kit
suitable for accelerating blood coagulation in blood without
requiring the use of additives.
2. Description of Related Art
[0002] After drawing blood from patients, coagulation of the fibrin
in blood is desirable in some circumstances, such as for analysis
of blood or for preparation of platelets and leucocyte-rich fibrin
patch. In these circumstances, it is desirable to complete fibrin
polymerisation as rapidly as possible to save processing time.
Furthermore, the coagulation speed differs from patient to patient,
and certain patients have blood which coagulates slowly, such as
patients on anticoagulant therapy drugs like Xarelto.RTM., Warfarin
or alike. For these patients with slow coagulation speed, the speed
may be so slow as to impede autologous treatment and/or reduce the
quality of blood clot and serum substantially thus reducing
treatment quality for potentially notably vulnerable patients and
increasing the risk of e.g. needing perpetual treatment.
[0003] For these reasons, there is a need for blood coagulation
accelerators and furthermore for blood collection equipment and
methods which provide an enhanced rate of blood coagulation without
leaving any soluble or particulate material in the serum layer or
in the clot after centrifugation thus avoiding potential
interference with clinical tests or contaminations when used
autologous, such as for blood testing/analysis and for production
of LeucoPatch.RTM. as disclosed in EP2334307B1.
[0004] US 2009/0162587 describes a vacuum blood collection
container useful for making a full blood draw from a patient, where
a full blood draw is 3.5 ml of blood. It describes that for example
to achieve a full blood draw for a vacuum tube of 7 ml, the
container would need an internal pressure of between 133 mBar and
400 mBar.
[0005] Known methods for accelerating and activating coagulation
include exposure to diatomaceous earth and particles of inorganic
silicates, and bio-chemicals such as ellagic acid and
thromboplastin. US 2003/0045857 discloses a coating for a blood
collection container having a compound of either thrombin,
heparinase and/or fibrinogen combined with diatomaceous earth
combining different procoagulant factors to create an effective
procoagulant environment. A problem with particulate activators is
that finely divided particles may not all adhere to the container
inner wall and may thus contaminate the serum layer and interfere
with certain blood uses. On the other hand, soluble biochemical
activators can be disadvantageous because these cannot be separated
easily from either the serum or blood clot and leave the blood
non-autologous. For specialised autologous applications, it is
unacceptable to have either soluble activators or particulates in
the cell mass of a blood clot.
[0006] In one line of commercial blood collection tubes, for
example a coating of silicate particles in polyvinylpyrrolidone
(PVP, a water-soluble polymer) is affixed to the inside of the
tube. When blood enters the tube, the PVP dissolves and silicate
particles are released to initiate clotting. This constitutes a
contamination of said blood for autologous uses.
[0007] EP0740155A1 discloses serum tubes coated with material that
activates the coagulation, but said coating material may not adhere
firmly to the serum tube surfaces and may therefore be carried
forward into subsequent process steps. This constitutes a
contamination of said blood sample which is as problematic as the
retention of chemical additives mentioned above.
[0008] EP0984279B1 discloses a method for accelerating blood
coagulation relying on the biochemical additives thrombin and/or
batroxobin. The resultant coagulated blood product may be useful
for certain clinical tests, but the additives make it
unsatisfactory for other uses such as autologous treatments.
[0009] EP 0 629 445 A2 discloses an evacuated blood collection
assembly including a plastic container having a plasma-treated
inside wall surface and an open end covered by a puncturable
septum.
[0010] U.S. Pat. No. 5,533,518 A discloses blood collection
assembly including a tube, which may be evacuated.
[0011] U.S. Pat. No. 5,326,535 A discloses a blood collection
container is coated on its inside wall with a unitarily immobilized
clotting activator. The activator may be applied to the surface by
an adhesive or by rendering the inside wall surface sticky with a
solvent and partially absorbing the activator into the sticky
surface.
[0012] The document "BD Vacutainer Evacuated Blood Collection
System" (November 2010) retrieved from the Internet:
URL:http://www.cliawaived.com/web/items/pd f/BD 367871 Blood
collection insert "2911file1.13df discloses tubes, needles and
holders used together as a system for the collection of venous
blood.
SUMMARY OF THE DISCLOSURE
[0013] A first object of the invention is to solve the
above-mentioned problems by providing a blood collection unit
suitable for accelerated blood coagulation of whole blood for
subsequent autologous or allogeneic use having an outer wall
comprising a closed bottom end, an open top end, a side wall
spanning between said ends, and a stopper for inserting in said
open end to releasably seal said blood collection container, the
stopper having a puncturable self-sealing septum (105) or valve, an
inner volume at least partially bounded by an inside surface of
said outer wall, and a procoagulant environment, wherein said inner
volume is prepared with a pressure of no more than 100 mBar.
[0014] The unit could e.g. be a blood collection container.
Alternatively, it could be a tube or a needle transporting the
blood sample from a blood-filled cavity, such as a patient, to the
blood collection container.
[0015] Thereby, blood coagulation is accelerated within the
container thus speeding up medical procedures dependent on
coagulation of blood absent of additives and contaminants which
would make the blood unsuited for certain uses, such as blood
testing/analysis and LeucoPatch.RTM.. A pure and uncontaminated
coagulated autologous blood product is achieved from a blood sample
significantly faster. When drawing blood without anticoagulant
additive, such as when taking serum samples or blood for
LeucoPatch.RTM. preparation, it is crucial to achieve fibrin
coagulation as rapidly as possible, especially when the blood
sample is taken form a patient on anticoagulant therapy drugs like
Xarelto.RTM., Warfarin or the like.
[0016] The roughness may be achieved by various methods. In one
embodiment, it is achieved by abrasion, such as sanding. In this
embodiment, it may be sanded by any grit sizes. Grits between 100
and 1,000 are useful, where grits such as between 300 and 600 may
be convenient.
[0017] Alternatively, it may be achieved by sparking, milling,
embossing or other ways that provide an uneven and/or jagged
surface. In an embodiment, the roughness is achieved by applying
the rough surface to the mould for casting the blood collection
containers. In an embodiment of the invention, the surface might be
provided by imprinting.
[0018] Roughness in the present context is related to surface
finish, surface texture, or surface topography. By roughness is
meant that the surface is non-smooth. This means, roughness is
height deviations in the direction of the normal vector of a real
surface from its ideal form. By an ideal form is meant a smooth
surface in the present context. If the height deviations are large,
the surface is said to be rough, whereas small height deviations
correspond to a smooth surface. A rough surface may be said to be
uneven or irregular.
[0019] By having a rough surface, the total surface area is larger
compared to a corresponding smooth surface since inevitably, the
height deviations introduce additional area. Roughness may be
quantified using various measures. Historically, the roughness
average R.sub.a has often been employed being the arithmetic
average of the absolute deviations measured from a common
reference. Another measure is the root mean square of the roughness
average R.sub.RMS being the root mean square, or standard
deviation, of the roughness average. From the calculation of
R.sub.RMS, e.g. a single large deviation within the non-smooth
surface will affect R.sub.RMS more than R.sub.a, since it weighs
such deviations more heavily.
[0020] When quantifying roughness within the present context, the
root mean square of the roughness average R.sub.RMS is
employed.
[0021] The container used may be produced in various materials.
Preferably, it is produced in a material such as PET, nylon type
polymers and other, preferably hydrophilic polymers. However, the
invention works well with the hydrophobic polymers as well.
Surprisingly, it has been found that the rough surface helps
activate coagulation/speed up coagulation of the blood. It is known
in the art that glass has a procoagulant effect on blood which has
been attributed to it being extremely hydrophilic. Further, it is
established in the art that plastics do not activate
coagulation/speed up coagulation which has been attributed to their
comparatively hydrophobic surfaces. However, with the increase of
surface area and/or uneven/sharp edges, this has been overcome.
[0022] In an embodiment, the activation site is located at the
bottom of the blood collection container. By providing the
activation site at the bottom of the blood collection container, it
allows the blood to impact/splash against the activation site
during the very initial blood draw. Further, the blood will be
pressed against the activation site during centrifugation,
enhancing the effect hereof.
[0023] In an embodiment, the activation site is located on the side
wall of the blood collection container.
[0024] In an embodiment, the activation site is located on both the
sidewall and at the bottom. In an embodiment, the activation site
covers the entire inside surface of the blood collection container
substantially. In an embodiment, the activation side covers the
entire inside surface of the blood collection container.
[0025] In an embodiment, the blood collection container comprises
an insert in its inner volume, where the activation site is located
on the insert.
[0026] In an embodiment, the insert comprises a float and a mesh.
In this embodiment, the float is adapted to lift the insert to the
top of the container at some time during or after centrifugation.
Lifting the float may depend on outside forces such as a device
pressing against the outside of the container until a predefined
pattern has been met, such as a sufficiently translucent/opaque
optical reading, when the blood sample is lit through. The mesh is
adapted to collect at least the fibrin fraction of the blood during
coagulation.
[0027] In an embodiment comprising an insert with a float and a
mesh, the activation site is located on the upper surface of the
float. Thereby, a surface is treated which is easy to access
compared to the sidewalls and bottom walls during production of the
blood collection container as it can be treated prior to being
inserted into the blood collection container. Further, this also
allows the blood to press against the activation site during
centrifugation and allows the blood to impact/splash against it
during the very initial blood draw.
[0028] In an embodiment, the activation site has a roughness of at
least 0.012 .mu.m, at least 0.025 .mu.m, at least 0.05 .mu.m, at
least 0.1 .mu.m, at least 0.2 .mu.m or at least 0.4 .mu.m.
[0029] In an embodiment, the activation site is hydrophobic.
[0030] In an embodiment, the inside surface is hydrophobic.
[0031] In an embodiment, the blood collection unit is made of a
hydrophobic material.
[0032] By the activation site, the inside surface, or the blood
collection unit being hydrophobic or being made from a hydrophobic
material is meant that water is repelled from the surface. Water is
a component of whole blood, especially of the blood plasma, thus
making it relevant to consider hydrophobicity. Physically,
hydrophobicity may be described and quantified using the contact
angle between a water droplet and the possible hydrophobic surface.
The contact angle for a hydrophobic surface may be larger than
90.degree. measured where the liquid vapour interface meets the
possible hydrophobic surface. The contact angle is the angle
between a tangent at a liquid vapour surface triple point and
measured towards the droplet. Thus, for a highly hydrophobic
material, the droplet is almost spherical, causing a large contact
angle, theoretically approaching 180.degree.. Thus, the activation
site, the inside surface, or the entire blood collection unit
repels a majority, i.e. the water contents, of the whole blood. By
repelling a majority of the whole blood, the activation site is
kept clean thereby maintaining procoagulant properties. If the
surface is not hydrophobic, clots may arise within the activation
site thereby preventing further coagulating processes within the
activation site.
[0033] In an embodiment, the inside surface has not been
corona-treated. Corona treatment, or plasma treatment, is known to
increase the surface area and to make the surface less hydrophobic
and is known in the art to activate coagulation. By avoiding corona
treatment, the activation of the coagulation process relies mainly
on the high roughness. The combination of high roughness and
corona-treated surface will result in improved activation, but the
effect of corona treatment may decrease with time.
[0034] In an embodiment, the blood collection unit is a tube or
double-ended needle. The tube and the double-ended needle may be
connected. Thereby, whole blood may be drawn from a first needle
end of the double-ended needle, e.g. connected to a patient, to a
second needle end of the double-ended needle. The coagulation
processes may be initiated during the transport of the whole blood
through an inner volume of the tube.
[0035] In an embodiment, the blood collection unit is a blood
collection container, wherein the outer wall comprises a closed
bottom end, an open top end, a side wall spanning between said ends
and a stopper for inserting in said open end to releasably seal
said blood collection container. The stopper has a puncturable
self-sealing septum or valve.
[0036] In an embodiment, the procoagulant environment further
comprises that the inner volume has been prepared with a pressure
of no more than 255 mBar. In an embodiment, the inner volume is
prepared with a pressure of no more than 200 mBar. In an
embodiment, the inner volume is prepared with a pressure of no more
than 130 mBar.
[0037] In an embodiment, the inner volume is prepared with a high
vacuum. This high vacuum could be a pressure of no more than e.g.
100 mBar, or no more than 200 mBar, or no more than 255 mBar.
[0038] In an embodiment, the activation site as a procoagulant is
combined with a high vacuum in the blood collection container prior
to blood draw which also serves as a procoagulant. This combination
serves to further decrease the total coagulation time. The initial
high vacuum will draw blood into the container faster than vacuums
used merely to facilitate the draw, such as the vacuums of
Vacutainer.RTM. of about 300 mBar. The blood entering the blood
collection enters with the highest speed initially and as the blood
fills the container, the pressure in the container will be slowly
normalised thus making the blood enter progressively slower. The
initial high speed of the blood in a container with above
conventional vacuum likely produces mechanical agitation of the
blood which activates the blood coagulation cascade.
[0039] Such high speed could also be obtained by other means than a
container with a vacuum, e.g. by initially drawing the blood into a
syringe and then applying pressure on the syringe piston, when
blood is filled into the device. Generally, the blood just needs to
be delivered, at least initially, to the interior of the container
with a high speed. This can e.g. be obtained with other means, e.g.
where there is a pressure difference between the source and the
destination of the blood.
[0040] Where the activation site is hit with an initial drop of
blood, the effect is even further increased as the blood is exposed
to the uneven surface with a greater force.
[0041] In an alternative embodiment, there is provided a blood
collection container suitable for accelerated blood coagulation for
subsequent autologous or allogeneic use of whole blood having an
outer wall comprising a closed bottom end, an open top end, a side
wall spanning between said ends, and a stopper for inserting in
said open end to releasably seal said blood collection container,
the stopper having a puncturable self-sealing septum or valve.
Inside the container there is an inner volume bounded by an inside
surface of said outer wall including said stopper. The blood
collection container further comprises a procoagulant environment,
wherein the procoagulant environment comprises said inner volume
(101) being prepared with a pressure of no more than 255 mBar.
[0042] The inventive method comprising creating and maintaining a
high vacuum environment inside the blood collection container has
the effect of accelerating blood coagulation of a blood sample
within said container thus speeding up medical procedures dependent
on coagulation of blood absent of additives and contaminants which
would make the blood unsuited for certain uses, such as blood
testing/analysis and LeucoPatch.RTM..
[0043] Thereby, a pure and uncontaminated coagulated autologous
blood product is achieved from a blood sample significantly faster
than previously possible. When drawing blood without anticoagulant
additive, such as when taking serum samples or blood for
LeucoPatch.RTM. preparation, it is crucial to achieve fibrin
coagulation as rapidly as possible, especially when the blood
sample is taken form a patient on anticoagulant therapy drugs like
Xarelto.RTM., Warfarin, or alike.
[0044] Any container capable of holding a vacuum is suitable for
use in the current invention. Most conveniently, a blood collection
container, which is suitable for generating and maintaining the
high vacuum of the current invention, is suitable.
[0045] In one embodiment, this is provided by a blood collection
kit of parts comprising a blood collection container. Said blood
collection container comprises a bottom wall, a side wall defining
an open end, and a stopper in said open end, said stopper further
comprising a puncturable self-sealing septum or valve, said
elements defining an inner volume of said container. The blood
collection container may be any container having a closed end and
an open end, for example bottles, vials, flasks and the like. Any
material or aggregate of materials capable of maintaining a high
vacuum with at least a transitory durability and suitable for
subsequent clinical use may be used in the blood collection
container, including but not limited to glass, polyethylene
terephthalate (PET) and/or polystyrene (PS).
[0046] In one embodiment of the invention, said blood collection
container is at least transitorily vacuum-durable.
[0047] Having a vacuum-durable blood collection container allows
the vacuum to better persist better over time which allows easier
handling and more efficient production, such as allowing an
industrially produced blood collection container to retain a vacuum
during subsequent processing and transport.
[0048] In one embodiment of the invention, a tube from a blood
container with anti-coagulated blood, for example a blood plastic
bag and bag systems, may be directly connected to a vacuum
device--preferably by a needle fitted on the tube.
[0049] In one embodiment of the invention, a part of the inner
surface of said bottom wall and/or a part of the inner surface of
said side wall of the blood collection container has been plasma
treated. In another embodiment, the entire inner surface of the
walls has been plasma-treated. Optionally, in either embodiment,
the inside of said stopper may also be plasma-treated. Likewise,
parts placed inside the container may also be plasma treated.
[0050] The plasma may be generated from any suitable process gas. A
representative but not limiting list of suitable process gases
includes nitrogen, ammonia, carbon dioxide, sulphur dioxide, air,
and oxygen, wherein air and oxygen are preferred. The tube may be
placed open end up between the electrodes of a conventional plasma
generator equipped with a pressure gauge, a gas inbleed, and a
vacuum connection. Suitable electrodes may be of any conducting
material, although stainless steel and aluminum are preferred. The
width and shape of the electrodes are not critical. Any suitable
ionising plasma may be used, as for example a plasma generated by a
corona discharge or a glow discharge. When a plasma is generated by
a corona discharge, the plasma treatment is commonly referred to as
corona treatment.
[0051] Likewise, atmospheric pressure plasma treatment or other
technologies used for surface treatment include in-line atmospheric
(air) plasma, flame plasma, and chemical plasma systems.
[0052] Alternatively or additionally, the insides may be abraded in
any convenient way. The surface may be roughened by any
conventional chemical or mechanical method, or during the
tube-forming process. Most conveniently, the surface is merely
rubbed with an abrasive, such as with sand or emery paper. No
limitation is placed on the grit of the abrasive.
[0053] Plasma treating and/or abrading increases surface area and
friction with the blood and is known in the art to activate
coagulation. Combining the high vacuum with another coagulation
activator useful for autologous use further increases coagulation
speed, blood product quality, and time for post-treatment care.
[0054] In an embodiment of the current invention, the blood
collection container having in its inner volume a high vacuum is
inserted into a first container or first container means
characterised in that it possesses at least transitory vacuum
durability and furthermore, that it can be subjected to a
sterilisation procedure and can retain at least transitory vacuum
durability. The first container means may take any shape,
preferably being a bag or sack, and may consist of any type of
material or aggregate of types of material. A representative but
not limiting list of materials would include plastics, cardboard,
glass, aluminium and/or aluminium foil. Said first container means
comprises at least one material affording it transitory vacuum
durability and furthermore allows sterilisation of said first
container means and its inner volume without degrading its vacuum
durability to less than a transitory vacuum durability, preferred
actual materials being dependent on sterilisation method. In a
preferred embodiment of the invention, the first container means
comprises at least polyethylene terephthalate (PET) or polystyrene
(PS).
[0055] Insertion into a first container means improves the
durability of the high vacuum inside the blood collection container
since now, the pressure drop from the outside air to the blood
collection container has to permeate two barriers. This improves
industrial applicability in a cost-efficient way since the blood
collection container does not have to be produced with
specifications to maintain its high vacuum during handling or
transport, but only during use.
[0056] In one embodiment of the invention, the first container
means containing the blood collection container has been
sterilised. Any method of sterilisation may be used, but typically
the most convenient techniques include heat (or heat and pressure)
sterilisation, chemical sterilisation, radiation sterilisation, or
any combination thereof. In a preferred embodiment, gamma-ray
sterilisation is utilised.
[0057] Sterilisation either before or after insertion into a first
container means is performed to significantly reduce risk of
contamination during clinical use of the blood collection container
and so to fulfil regulatory and safety requirements.
[0058] Because the high vacuum imposes a higher pressure
differential on the blood collection container of this invention
when compared to blood collection containers of the art,
contaminations are more likely to be introduced simply by power of
diffusion through imperfections in its construction, materials
and/or seams. By inserting the blood collection container into a
first vacuumed container means and sterilising it inside this said
first vacuumed container means, the likelihood of any partial
depressurisation and its associated risk of contamination of the
inside of the blood collection container is eliminated or
reduced.
[0059] In one embodiment of the invention, sterilization of the
first container means containing the blood collection container is
followed by inserting the first container means containing the
blood collection container into a second container means,
characterised in that said second container maintains a vacuum
substantially durably, said second container means is then emptied
of air and sealed. Preferably, said second container means
comprises at least one material enabling said second container
means to maintain a vacuum substantially durably. Said second
container means may consist of any type of material or aggregate of
types of material, a representative but not limiting list of
materials would include plastics, cardboard, glass and/or
aluminium. In a preferred embodiment of the invention, the second
container means comprises at least aluminium or aluminium foil.
[0060] Sterilising the blood collection container inside the first
container means with limited vacuum durability, which is unfit for
long-time storage, provides a transitory vacuum durability even
through sterilisation. To increase vacuum durability, the first
container means containing the blood collection container is
inserted into a second container means chosen for substantial
vacuum durability and handling durability.
[0061] This dual-sealing allows a blood collection container to be
produced which meets regulatory and safety requirements while
attaining and maintaining a substantially durable vacuum through
transportation and storage in a way that meets economic and
industrial specifications.
[0062] In an embodiment of the invention, the blood collection
container is sterilised before insertion into the first container
means.
[0063] With a sufficiently high quality blood collection container,
said high quality pertaining to it being substantially vacuum
durable after a sterilisation procedure, it may not be necessary to
dual-seal it to achieve the desired sterility and vacuum
durability. Sealing it once and doing so after sterilisation is
then sufficient for handling and vacuum durability purposes.
[0064] The blood collection container may be prepared with a high
vacuum at any convenient time prior to, or during blood draw. An
inexhaustible list of times is during manufacture and at a time
prior to drawing blood recognising the vacuum durability of the
used blood collection container ensuring that at least a high
vacuum remains when drawing blood. In an embodiment of the
invention, it is important to expose the blood to the high vacuum
during blood draw to stress the blood cells significantly and so to
initiate and/or accelerate coagulation.
[0065] The high vacuum of the blood collection container may be
prepared in any convenient way, such as by using a vacuum pump.
Likewise, the vacuums of the first and second container means may
be applied in any convenient way.
[0066] In one embodiment of the invention, the blood coagulation
inside the first blood collection container is further accelerated
by at least one coagulation-accelerating object inside of it which
accelerates blood coagulation through this exposure. For example,
it may expose the blood to one or more glass surfaces, glass having
been known in the art for a long time to promote coagulation. Such
objects may be one or more glass beads.
[0067] By exposing the blood to a further coagulating agent, the
coagulation time can be further decreased thus ensuring the
shortest possible process time and so increasing time for
post-treatment care.
[0068] The blood may be drawn into the blood collection container
by any means used in the art. In one embodiment of the invention,
the blood collection kit of parts further comprises a double-ended
needle for drawing blood from a patient into the first blood
collection container comprising a first needle-end, a second
needle-end, and an intermediate tube, said double-ended needle
comprising an inner volume running the axial length of the
double-ended needle possibly with a fixed low inner volume of the
double-ended needle system compared to the volume in the blood
collection chamber in order to limit the depressurisation of the
blood collection container during use.
[0069] In one embodiment of the invention, a first needle-end of
said double-ended needle first enters a convenient blood-filled
cavity, typically of a patient and preferably a vein of said
patient. After the first needle end has entered its designated
blood-filled cavity, a second needle end punctures the puncturable
septum of the blood collection container. Then, the vacuum inside
the inner volume of the blood collection container draws the blood
from the patient by way of a pressure differential.
[0070] In an embodiment, the double-ended needle comprises an
inside procoagulant environment. Thereby, the blood coagulation may
be activated already when passing through the tube. In an
embodiment, the procoagulant environment in the double-ended needle
comprises an activation site with a high roughness.
[0071] Alternatively, collected blood may be removed from a blood
container and may even be divided into smaller volume samples, some
of which can also be used for different purposes or stored for
later use.
[0072] In one embodiment of the invention, the first needle end may
enter a previously filled second blood container instead of
directly entering a patient. This allows potentially easier
handling of the blood as well as drawing blood once and using it
multiple times thus decreasing the number of times the skin of the
patient needs to be penetrated among other advantages.
[0073] In one embodiment of the invention, the inner volume
contains components adapted to counteract anti-coagulants added to
the blood, such as calcium, at a level sufficient to counteract the
activity of the anti-coagulants.
[0074] In another embodiment of the invention, the double-ended
needle may be a catheter inserted into the circulatory system of a
patient.
[0075] In one embodiment of the invention, the inner volume defined
by the inner surface of the double-ended needle is such that
bringing it into fluid communication with the inner volume of the
blood collection container retains the high vacuum in the interior
of the blood collection container. Consequently, this builds a high
vacuum in the inner volume of the double-ended needle.
[0076] Achieving this combined high vacuum requires a comparatively
higher initial vacuum in the blood collection container as well as
a controlled volume of the double-ended needle, both taken together
ensuring a controlled depressurisation before exposure to the
blood. However, the balance of these two may take any form. For
example, creating an extremely high vacuum in a large blood
collection container allows a comparatively larger double-ended
needle and conversely, a double-ended needle with a small volume
will allow a lower grade vacuum and/or a smaller blood collection
container.
[0077] In one embodiment of the invention, the double-ended needle
has a fixed low inner volume V.sub.r or V.sub.a so as to limit the
depressurisation of the blood collection container during use. For
example, with a double-ended needle volume of 10% of the blood
collection container of 100 ml and a prepared initial vacuum of
99%, the combined volume being 110 ml would hold 11 ml of air or
90% vacuum. Thus, a low inner volume of the double-ended needle
ensures that the vacuum exerts a comparatively greater effect on
the blood sample thus speeding up the coagulation and so increasing
time for post-treatment care.
[0078] Another method to increase the pressure difference is to
draw the blood into a syringe initially and then apply pressure on
the syringe piston when blood is filled into the device.
[0079] In another embodiment of the invention, the double-ended
needle has a membrane or pressure valve to control the flow of
blood after injecting the first needle end into typically a vein
and before inserting the second needle end into a blood collection
container. It is then for example the pressure differential of
bringing the two inner volumes into fluid communication that breaks
or opens the membrane or opens the valve.
[0080] In one embodiment of the invention, the double-ended needle
further comprises coagulation accelerating objects in its inner
volume. By exposing the blood to coagulation activating objects
here, process time is further decreased.
[0081] In an embodiment of the invention, the blood collection
container further comprises an activation site formed in the inside
surface, the activation site having a high roughness.
[0082] In an embodiment of the invention, the activation site has a
roughness of at least 0.012 .mu.m.
[0083] In an embodiment of the invention, the activation site is
hydrophobic.
[0084] In an embodiment of the invention, the inside surface is
hydrophobic.
[0085] In an embodiment of the invention, the blood collection
container is made of a hydrophobic material.
[0086] In the above, a vacuum container has been described, where
one effect is the resulting high speed with which the blood is
delivered to the container. Such high speed could also be obtained
by other means than a container with a vacuum, e.g. by initially
drawing the blood into a syringe and then applying pressure on the
syringe piston, when blood is filled into the device. Generally,
the blood just needs to be delivered, at least initially, to the
interior of the container at high speed. This can be obtained with
other means, where there is a pressure difference between the
source container and the destination container of the blood.
BRIEF DESCRIPTION OF THE DRAWINGS
[0087] In the following, example embodiments are described
according to the invention, where
[0088] FIG. 1 is a side view of the evacuated blood collection
container means according to the present invention;
[0089] FIG. 2 is a view of the evacuated blood collection container
means inserted into a first vacuum-sealed container means according
to the present invention;
[0090] FIG. 3 is a view of the evacuated blood collection container
means inserted into a first vacuum sealed container means inserted
into a second vacuum sealed container means according to the
present invention;
[0091] FIG. 4 is a side view of the blood collection container
means while drawing blood through a double-ended needle.
[0092] FIG. 5 details measurement data demonstrating the effects of
degrees of vacuum on coagulation of blood.
[0093] FIG. 6 illustrates various blood coagulation containers with
roughened inside surfaces.
[0094] FIG. 7 illustrates readings during a controlled experiment
of a rough inside surface.
[0095] FIG. 8 illustrates the effect of combining high vacuum and
rough surface.
DETAILED DESCRIPTION OF THE DISCLOSURE
[0096] In the following, the invention is described in detail
through embodiments thereof that should not be thought of as
limiting to the scope of the invention.
[0097] FIG. 1 describes a side view of a blood collection container
100 comprising a bottom wall 102 and a side wall 103 forming a
container with an open end and a closed end. A stopper 104 is
fitted in said open end, said bottom wall 102, side wall 103 and
stopper 104 enclosing an inner volume 101 of said blood collection
container 100, said stopper comprising at least a mechanism for
securely sealing said open end and maintaining a pressure
differential, in a preferred embodiment making the blood collection
container at least transitorily vacuum durable. Said stopper 104
further comprises a self-sealing puncturable septum 105 or a valve
allowing the emptying of air from the inner volume 105 through any
convenient method, such as a vacuum pump, said self-sealing
puncturable septum 105 or valve further allowing the insertion of a
needle or other tube-end without simultaneously allowing
atmospheric air into the inner volume 101. This allows passage of
blood through a needle into the blood collection container while
maintaining a high vacuum in the inner volume 101.
[0098] Further depicted in FIG. 1 is an inner surface of said
bottom wall 106, an inner surface of said side wall 107, and an
inner surface of said stopper 108, said inner surfaces all facing
and being in contact with said inner volume 101. These or some of
these surfaces may be plasma-treated and/or abraded to accelerate
coagulation speed further.
[0099] The blood collection container is prepared for use by
inserting the stopper into its designated position in the open end
of the blood collection container 100 and emptying the blood
collection container of air through the self-sealing puncturable
septum 105 or valve, said emptying of air further securing said
stopper in its position by exerting a downward pressure due to the
pressure differential over said stopper.
[0100] FIG. 2 is a side view of a blood collection container 100
inside a vacuum-sealed first container means 200, said first
container means being at least transitorily vacuum durable, said
blood collection container comprising a bottom wall 102, a side
wall 103 defining a container with an open and a closed end, and a
stopper 104 in said open end, said stopper further comprising a
puncturable septum 105 or a valve for emptying the enclosed inner
volume 101 of air thus creating a high vacuum, said puncturable
septum or valve further allowing drawing blood into the blood
collection container without simultaneously allowing atmospheric
air into the inner volume 101.
[0101] The blood collection container is inserted into the first
container means 200 which is emptied of air thus ensuring that it
encloses said blood collection container tightly, whereupon said
first container means is vacuum-sealed thus lowering the pressure
differential over the bottom wall, side wall, and stopper of said
blood collection container thus improving the effective vacuum
durability of said blood collection container. Any convenient
sealing method may be used and in one embodiment, when a convenient
vacuum has been achieved inside the first container means, it is
heat-sealed at the sealing line 201.
[0102] FIG. 3 is a side view of a vacuum-sealed second container
means 300 being substantially vacuum-durable, said second container
means comprising a first container means 200 further comprising a
blood collection container prepared with a high vacuum.
[0103] The three containers taken together, i.e. the blood
collection container, the first container means 200, and the second
container means 300, make up a blood collection kit of parts
prepared for transportation, storage and handling.
[0104] Preferably, a first container means 200 vacuum-sealed and
comprising a blood collection container is sterilised, whereupon it
is inserted into a second container means 300, said second
container means then being emptied of air thus ensuring that it
encloses said first container means tightly, whereupon said second
container means is vacuum-sealed thus lowering the pressure
differential over the enclosed vacuum barriers and improving the
effective vacuum durability of said blood collection container. In
one embodiment, when a convenient vacuum has been achieved inside
the second container means such as a high vacuum, it is heat sealed
at the sealing line 301.
[0105] FIG. 4 is a side view of a blood collection kit of parts
4000, the kit of parts comprising a blood collection container 100
and a double-ended needle 400 after drawing blood from a patient
and disassembling the kit of parts for further processing of the
blood.
[0106] The blood collection container 100 comprises a bottom wall
102, a side wall 103 defining a container with an open and a closed
end, and a stopper in said open end, said stopper further
comprising a puncturable septum 105 or a valve for emptying the
enclosed inner volume 101 of air thus creating a high vacuum, said
puncturable septum or valve further allowing drawing blood into the
blood collection container without simultaneously allowing
atmospheric air into the inner volume 101. The blood collection
container further comprises a blood sample 405.
[0107] The double-ended needle comprises a first needle end 401, a
second needle end 402, an intermediate tube 403, and an inner
volume 404 running the axial length of said double-ended needle,
the inner volume allowing the transport of blood from the patient
to the blood collection container. In one embodiment of the
invention, the inner volume further comprises coagulation
accelerating objects, such as one or more glass beads.
[0108] In another embodiment of the invention, the double-ended
needle further comprises a membrane or pressure valve controlling
the flow of blood after injecting the first needle end into a
blood-filled cavity such as the vein of a patient and prior to
inserting the second needle-end into the blood collection
container.
[0109] In one embodiment of the invention, the blood collection kit
of parts further comprises a first container means 200 and a second
container means 300.
[0110] A high vacuum may be introduced into the blood collection
container by any convenient method. Preferably a blood collection
kit of parts 4000 is unpackaged thus allowing access to the blood
collection container 100 from within a first and a second container
means, the blood collection container being previously prepared
with a high vacuum. Then the first needle head 401 enters a
convenient volume of the patient, typically a vein, whereupon blood
begins running through the inner volume 404 of the double ended
needle and simultaneously blocking fluid communication from the
blood collection container to outside ambient pressure through the
double-ended needle at the first needle end 401. In another
embodiment, a membrane or pressure valve at a convenient location
inside the double-ended needle, preferably close to the second
needle-end, blocks the flow of blood prior to bringing the two
inner volumes 101, 404 into fluid communication. This allows easier
handling by not needing as careful handling and observation to
ensure the blood does not run out of the second needle end prior to
puncturing the self-sealing septum as well as a controlled and
limited depressurisation as consequence of bringing the two inner
volumes into fluid communication since the blood will have pushed a
certain controlled, preferably high amount of the air out of the
double-ended needle. For example, this membrane or valve comprises
rubber or another convenient material. Bringing the inner volumes
into fluid communication breaks or opens the membrane or opens the
valve and allows the blood to flow.
[0111] In the case of using a double-ended needle with a membrane,
valve or without either, a second needle end 402 then punctures the
self-sealing septum of a blood collection container 100 which
brings the high vacuum inner volume of the blood collection
container 101 into fluid communication with the inner volume of the
double-ended needle 404, this fluid communication decreasing the
pressure in the inner volume of the double-ended needle 404 and so
actuates an accelerated blood draw.
[0112] FIG. 5 is measurement data of the various effects on
coagulation speed by using 90% (101 mBar), 92% (81 mBar) and 98%
(20 mBar) vacuum in a blood collection container during blood
filling, Thereafter inserted into a centrifuge, where the
coagulation process is observed by way of the translucency of the
top part of the blood sample.
[0113] In a first phase, translucency increases continually as the
blood separates and blood plasma remains in the uppermost part due
to it comprising elements relative to the rest of the blood lower
Svedberg values, which means forces like gravity, and the
centripetal force acts less strongly on these elements and may be
thought of as an alternative property to mass for the sake of this
invention.
[0114] In a second phase, fibrin in the blood plasma begins
polymerising thus reducing translucency as the blood plasma becomes
more opaque. This reduces transmission counts. Table 1 describes
the events shown in FIG. 5:
TABLE-US-00001 TABLE 1 90% 92% 98% peak transmission count at 7.94
minutes 7.45 minutes 6.91 minutes post-peak lowest transmission
9.93 minutes 8.74 minutes 7.62 minutes count at
[0115] FIG. 6 illustrates various embodiments of the invention. All
embodiments shown in FIG. 6 illustrate a blood collection container
as previously described with a bottom wall 102, an open end with a
stopper 104, and a sidewall spanning between 103. The stopper has a
self-sealing septum 105.
[0116] The inside surface of the blood collection container 100 is
provided with an activation site 600. In FIG. 6a, the bottom
surface is provided with an activation site 600. The activation
site has a high roughness average (R.sub.a) which has been found to
increase coagulation speed significantly. By providing the
activation site 110 at the bottom of the blood collection container
100, the blood will be pressed against it during centrifugation
thus enhancing the effect hereof.
[0117] FIG. 6b illustrates an embodiment, where the activation site
600 is provided on the sidewall. The embodiments shown in FIGS. 6a
and 6b may be combined to provide more activation sites and/or
spreading these around in the blood collection container 100.
[0118] FIG. 6c illustrates an embodiment of the invention, where
the activation site 600 is provided in an insert 602. The
illustrated insert is a float which has an inner volume with a
lower density than blood thus allowing lifting the float during or
after centrifugation. Thereby, as the blood travels through the
central hole 604 to beneath the float 602 during lifting the float
602, the blood will move over the activation site 600 on the insert
602 and thus expose more blood to the activation site 602. There
may be provided any kind of channels through or next to the insert
in accordance with the invention.
[0119] FIG. 6d illustrates a double-ended needle 400 mostly as
previously described. The double-ended needle 400 has on its inner
surface 406 an activation site 600' that is an area with a high
roughness. As the blood passes the activation site 600', the
coagulation cascade is initiated. This allows early and thorough
coagulation activation.
[0120] Generally, the inner surface of the collection unit being
the double-ended needle or the container should at least partly
have a surface with a high roughness (activation site), whereby the
surface is non-smooth, and where this non-smooth surface influences
the coagulation speed. As mentioned above, the non-smooth surface
could be provided on the sidewalls or bottom walls of the container
itself or it could be provided on inserts positioned in the
container.
[0121] The inner surface of a plastic container could e.g. be made
non-smooth to increase the roughness by abrading the surface e.g.
using abrading machinery or manually using abrading material.
[0122] FIG. 7 shows a controlled experiment of the effect of a
rough surface on blood coagulation 710, even when the surface is of
a hydrophobic material. The experiment measured optical
transmittance 714 and RPM of the centrifuge 716 as functions of
time 712.
[0123] The experiment was conducted on two identical samples. One
was exposed to a rough inside surface, the test sample 720, 720'
and the other were not exposed to a rough inside surface, i.e. the
control sample 724, 724. Centrifuge work speed 728 was also
measured. The variance between 720 and 724 on the one side and 720'
and 724' on the other side is due to two sensor locations of the
container during centrifugation.
[0124] The optical transmittance 714 changes during the experiment
as a result of the coagulation. At first, when the blood is still
mixed and in liquid form, the optical transmittance is low as light
cannot penetrate the blood. During centrifugation, the blood is
separated into several layers--at first a plasma layer at the top
being yellowish transparent, a buffy coat layer being a more opaque
white in the middle, and a dark red layer of erythrocytes (red
blood cells) at the bottom. These layers emerge as the heavier
molecules are drawn to the bottom of the blood collection
container. Subsequently, fibrin gradually polymerises from the
plasma layer and descends onto the buffy coat layer. Without the
fibrin, the top layer is then serum which is even more transparent
than plasma. The polymerised fibrin is an opaque yellowish
white.
[0125] The optical transmittance 714 is measured at the top of the
container in what becomes the plasma fraction during
centrifugation. Therefore, the optical transmittance increases
steadily as heavy and generally light-absorbing molecules descend.
This is initially comparative between the test sample 720 and the
control sample 724. However, the translucency drops off for the
test sample 720 earlier than for the control sample 724 thus
indicating that fibrin is polymerising significantly earlier due to
the rough surface.
[0126] FIG. 8 shows a controlled experiment of the effect of
combining a high vacuum with a rough surface on blood coagulation
810. The experiment measured optical transmittance 814 as function
of time 812. The blood considered has been exposed to
centrifugation during the time considered. Thus, the optical
transmittance 814 changes during the experiment as a result of the
coagulation taking place during centrifugation. The process of
coagulation and its impact on optical transmittance 814 is
identical to the one described in FIG. 7.
[0127] The experiment of FIG. 8 was conducted on four identical
whole blood samples. The samples were drawn into four different
blood collection containers all comprising different environments:
The first sample 831 was exposed to a vacuum of 80% (202.65 mBar),
the second sample 832 was exposed to a vacuum of 98% (20.27 mBar),
the third sample 833 was exposed to a vacuum of 80% (202.65 mBar)
and a surface comprising an activation site having a high
roughness, and the fourth sample 834 was exposed to a vacuum of 98%
(20.27 mBar) and a surface comprising an activation site having a
high roughness.
[0128] Considering first the samples exposed to vacuum only, the
optical transmittance 814 of both the first 831 and the second 832
samples are seen to increase steadily and comparatively. However,
the optical transmittance 814 drops off for the second sample 832
earlier than the first sample 831 thus indicating that fibrin is
polymerising, i.e. coagulation is taking place significantly
earlier in the high vacuum of the second sample 832 than for the
first sample 831 comprising a relatively lower vacuum.
[0129] Considering the third 833 and the fourth 834 sample, both
being exposed to an activation site having a high roughness, the
optical transmittance 814 is seen to increase steadily and
comparatively at first. However, it is seen that the fourth sample
834, which is further exposed to a relatively higher vacuum (98%,
20.27 mBar) than the third sample 833, drops off earlier than said
third sample which is exposed to a relatively lower vacuum (80%,
202.65 mBar) than the fourth sample 834. Furthermore, it is seen
that the fourth sample 834 coagulates earlier than the second
sample 832 despite both being exposed to the same vacuum. The same
is seen for the third sample 833 coagulating earlier than the first
sample 831.
[0130] Thus, from the experiment 810, it is seen partly that a high
vacuum causes faster coagulation of blood than a relatively lower
vacuum and partly that a surface comprising an activation site
having a high roughness causes coagulation faster than a surface
not comprising such activation site. Most importantly, it is
further seen that the combination of a high vacuum (98%, 20.27
mBar) and a surface comprising an activation site having a high
roughness (i.e. the fourth sample 834) causes coagulation of blood
before any other combinations (the first 831, the second 832, and
the third 833 sample).
[0131] High Vacuum=A pressure of no more than 255 mBar, 253.31
mBar, 202.65 mBar, 151.99 mBar, 101.33 mBar, 91.19 mBar, 81.06
mBar, 70.93 mBar, 60.80 mBar, 50.66 mBar, 40.53 mBar, 30.40 mBar,
20.27 mBar, 10.13 mBar, 5.07 mBar, 1.01 mBar, 0.10 mBar or less,
and where the preferable range of pressure is 0.10 mBar-101.33 mBar
or less.
[0132] In another embodiment of the invention, said high vacuum
corresponds to a vacuum of at least 75% (253.31 mBar), 76% (243.18
mBar), 77% (233.05 mBar), 78% (222.92 mBar), 79% (212.78 mBar), 80%
(202.65 mBar), 81% (192.52 mBar), 82% (182.39 mBar), 83% (172.25
mBar), 84% (162.12 mBar), 85% (151.99 mBar), 86% (141.86 mBar), 87%
(131.72 mBar), 88% (121.59 mBar), 89% (111.46 mBar), 90% (101.33
mBar), 91% (91.19 mBar), 92% (81.06 mBar), 93% (70.93 mBar), 94%
(60.80 mBar), 95% (50.66 mBar), 96% (40.53 mBar), 97% (30.40 mBar),
98% (20.27 mBar), 99% (10.13 mBar), 99.5% (5.07 mBar), 99.9% (1.01
mBar) or even 99.99% (0.10 mBar) or above as measured linearly,
where 0% vacuum is 1013.25 mBar and 100% vacuum is 0 mBar, and
where the preferable range of vacuum is 90%-99.99% or above.
[0133] V.sub.r, is a relatively defined inner volume 404 of a
double-ended needle 400=1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10% or
less relative to the volume of the blood collection container
100.
[0134] V.sub.a, is an absolutely defined inner volume of the
double-ended needle, where it corresponds to V.sub.r for a blood
collection container of 10 ml=0.1 ml being 1% of 10 ml, 0.2 ml, 0.3
ml, 0.4 ml, 0.5 ml, 0.6 ml, 0.7 ml, 0.8 ml, 9 ml or 1.0 ml being
10% of 10 ml. Vacuum Durability=a quality of a boundary enclosing
an environment defining its ability to maintain a percentage of a
pressure differential over said boundary over time, specifically
where there is a pressure drop from the exterior to the enclosed
environment. Two distinct degrees of vacuum durability is
described; transitory vacuum durability and substantial vacuum
durability, where:
[0135] A boundary with a transitory vacuum durability maintains at
least 10% of its pressure differential over 24 hours, 48 hours, 72
hours, 96 hours, 120 hours, 144 hours, 168 hours or more, where the
initial pressure inside the enclosed environment is a high vacuum
and relative to 1013.25 mBar at ambient temperature outside.
[0136] A boundary with a substantial vacuum durability maintains at
least 98% of its pressure differential over 1 week, 2 weeks, 3
weeks, 4 weeks, 6 weeks, 8 weeks, 12 weeks or more, where the
initial pressure inside the enclosed environment is a high vacuum
and relative to 1013.25 mBar at ambient temperature outside.
[0137] Blood collection container=a container specifically designed
for storage and collection of blood immediately after drawing blood
from a patient. Such blood collection containers may be used in
subsequent treatment of the blood such as in producing
LeucoPatch.RTM., or it may only be used for transportation and
storage of the blood for later use. Blood collection containers are
most conveniently produced in glass, polyethylene terephthalate
(PET) and/or polystyrene (PS).
[0138] Double-ended needle=typically a tube with a needle in both
ends, preferably being able to puncture skin and a vein in the one
end and a puncturable septum in the other end. In other embodiments
of the invention, the double-ended needle may be regarded as any
tube the ends of which are injected into an upstream blood-filled
cavity, such as a vein or a blood container, and a downstream blood
collection container despite the ends not being actual needles, the
term double-ended needle encompassing catheters and tubes as well.
Double-ended needles are conveniently produced in silicone,
polyurethane, polyethylene and/or Teflon/PFTE.
A. A blood collection container (100) having a bottom wall (102)
and a side wall (103) defining an open end, a stopper (104) in said
open end, said stopper (104) further comprising a puncturable
self-sealing septum (105) or valve, said elements defining an
interior volume (101) of said blood collection container (100),
characterised in that the interior volume (101) has been prepared
with a pressure in its inner volume (101) of no more than 255 mBar.
B. A blood collection container (100) according to embodiment A,
wherein said inner volume (101) is prepared with a pressure of no
more than 200 mBar. C. A blood collection container (100) according
to any of embodiments A-B, wherein said inner volume (101) is
prepared with a pressure of no more than 130 mBar. D. A blood
collection container (100) according to any of embodiments A-C
capable of retaining at least 10% of the pressure differential
between the high vacuum in its inner volume (101) relative to
ambient temperature and pressure on the outside after 24 hours. E.
A blood collection container (100) according to any of embodiments
A-D further comprising components adapted to counteract
anti-coagulants added to the blood, such as calcium, inside the
blood collection container (100). F. A blood collection container
(100) according to any of embodiments A-E, where at least part of
the inner surfaces (106, 107, 108) of said blood collection
container (100) surrounding the inner volume (101) are
corona-treated. G. A blood collection container (100) according to
any of embodiments A-F further comprising a blood coagulation
acceleration agent inside the blood collection container (100). H.
A blood collection container (100) according to any of embodiments
A-G further comprising an activation site (600) formed in the
inside surface (106, 107, 108), the activation site having a high
roughness. I. A blood collection container (100) according to
embodiment H, where the activation site (600) has a roughness of at
least 0.012 .mu.m. J. A blood collection container (100) according
to any of embodiments H-I, where said activation site is
hydrophobic. K. A blood collection container (100) according to any
of embodiments H-J, where the inside surface (106, 107, 108) is
hydrophobic. L. A blood collection container (100) according to any
of embodiments H-K made of a hydrophobic material. M. A blood
collection kit of parts (4000) comprising a blood collection
container (100) for accelerated coagulation of blood according to
any of embodiments A-L, wherein said kit of parts further comprises
a first container means (200) and a second container means (300),
said second container means (300) being capable of retaining at
least 98% of the pressure differential between the vacuum in its
inner volume relative to ambient temperature and pressure on the
outside after one week, the second container means (300) vacuum
being sealed around said first container means (200) which is
capable of retaining at least 10% of the pressure differential over
its enclosing walls after 24 hours, the first container means (200)
being vacuum-sealed around said blood collection container (100).
N. A blood collection kit of parts (4000) according to embodiment
M, where the first container means (200) comprises PS and/or PET
and the second container means (300) comprises aluminium or
aluminium foil. O. A blood collection kit of parts (4000)
comprising a blood collection container (100) for accelerated
coagulation of blood according to any of embodiments A-N further
comprising a double-ended needle (400) comprising a first needle
end (401), a second needle end (402), an intermediate tube (403),
and an inner volume (404) running the axial length of said
double-ended needle (400), where the combination of the degree of
vacuum prepared in said inner volume of the blood collection
container (101) and said inner volume of said double-ended needle
(404) is such that bringing the two inner volumes (101, 404) into
fluid communication retains a pressure of no more than 255 mBar,
preferably no more than 200 mBar, even more preferably no more than
130 mBar inside the combined inner volumes (101, 404). P. A blood
collection kit of parts (4000) according to embodiment 0, wherein
said double-ended needle (400) further has a procoagulant
environment (404).
[0139] A blood collection kit of parts (4000) according to
embodiment P, wherein said procoagulant environment comprises an
activation site (600') on an inner surface (406) of said
double-ended needle (400) having a high roughness.
* * * * *
References